Studies are being carried out to determine the influence of major histocom- patibility complex (MHC) genes and gene products on disease progression in individuals infected with retroviruses. The MHC is located on the human chromosome 6 and encodes for cell surface proteins classically known as transplantation or HLA antigens. Class I antigens (HLA-A,B,C) are expressed on all cells of the body, and the class II antigens (HLA-DR,DQ) are expressed on B lymphocytes, monocytes/macrophages as well as on activated T lymphocytes, endothelial cells, and some tumor cells. Functionally, these cell surface molecules play an integral role in regulating both the afferent and the efferent pathways of the immune response. Since the retroviruses HIV-1 and HTLV-I infect macrophages and lymphocytes, it seems likely that the cell surface structures with polymorphic HLA determinants may play a role in regulating infection and disease progression. HLA serologic typing was performed on a cohort of 89 homosexual men with a prevalent AIDS diagnosis, 47 individuals with Kaposi's sarcoma (KS), 27 individuals with opportunistic infection (OI), and 15 individuals with KS and OI. Also typed were the following cohorts of homosexual men and hemophiliacs who were HIV-1 seroprevalent. Homosexual men: 112 HIV-1 seronegative, 123 HIV seropositive, 6 of whom have developed KS, and 49 OI over a mean follow-up period of 5 years. Hemophiliacs: 129 seronegative, 265 HIV-1 seropositive, and of the 265, 22 have developed AIDS. While HLA serological typing identifies antigenic polymorphism, more extensive polymorphisms are known to be present in the genes that encode these molecules. Thus HLA typing can also be performed at the DNA level using specific oligonucleotide probes and the polymerase chain reaction. Oligonucleotide probes have been developed to detect the polymorphic alleles for DQ beta and DQ alpha. Using these techniques, studies are underway to investigate the populations of HIV-infected individuals with a particular disease outcome where serologic typing indicates that there is an association of a particular HLA phenotype with the disease.